F
IPR000380

DNA topoisomerase, type IA

InterPro entry
Short nameTopo_IA
Overlapping
homologous
superfamilies
 
family relationships

Description

This entry describes the type IA topoisomerases, which are highly conserved enzymes that are structurally distinct from type IB enzymes. The structures of both topoisomerases I and III have been elucidated, and consist of four domains that together form a toroidal molecule with a central hole that is large enough to accommodate single- and double-stranded DNA
[4]
. It is believed that the domains transiently separate from one another to allow the entrance and exit of DNA strands.

DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single-or double-strand breaks, crossing the strands through one another, then resealing the breaks
[10]
. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis
[2, 9]
. DNA topoisomerases are divided into two classes: type I enzymes (
5.6.2.2
; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
5.6.2.2
; topoisomerases II, IV and VI) break double-strand DNA
[3]
.

Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB
[1]
. They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases
[5, 8]
. The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases
[6, 7]
.

References

1.Origin and evolution of DNA topoisomerases. Forterre P, Gribaldo S, Gadelle D, Serre MC. Biochimie 89, 427-46, (2007). View articlePMID: 17293019

2.Cellular roles of DNA topoisomerases: a molecular perspective. Wang JC. Nat. Rev. Mol. Cell Biol. 3, 430-40, (2002). View articlePMID: 12042765

3.Phylogenomics of type II DNA topoisomerases. Gadelle D, Filee J, Buhler C, Forterre P. Bioessays 25, 232-42, (2003). View articlePMID: 12596227

4.The mechanism of type IA topoisomerase-mediated DNA topological transformations. Li Z, Mondragon A, DiGate RJ. Mol. Cell 7, 301-7, (2001). View articlePMID: 11239459

5.Topoisomerases and site-specific recombinases: similarities in structure and mechanism. Yang W. Crit. Rev. Biochem. Mol. Biol. 45, 520-34, (2010). View articlePMID: 21087076

6.[The structure and mechanism of the action of type-IB DNA topoisomerases]. Bugreev DV, Nevinskii GA. Bioorg. Khim. 36, 293-311, (2010). View articlePMID: 20644584

7.Human DNA topoisomerase IB: structure and functions. Cretaio E, Pattarello L, Fontebasso Y, Benedetti P, Losasso C. Ital. J. Biochem. 56, 91-102, (2007). PMID: 17722649

8.Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA. Redinbo MR, Stewart L, Kuhn P, Champoux JJ, Hol WG. Science 279, 1504-13, (1998). View articlePMID: 9488644

9.DNA topoisomerases: structure, function, and mechanism. Champoux JJ. Annu. Rev. Biochem. 70, 369-413, (2001). View articlePMID: 11395412

10.The mechanisms of DNA topoisomerases. Roca J. Trends Biochem. Sci. 20, 156-60, (1995). View articlePMID: 7770916

GO terms

Cross References

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